Accessing Core-Functionalized DNA–Polymer Nanostructures via RAFT Polymerization-Induced Self-Assembly

DNA–polymer nanostructures with precise sequences and programmable recognition capabilities are capable of achieving spatially accurate organization of functional moieties for applications in targeted drug delivery, biosensing, bioimaging, and regenerative medicine. However, traditional synthetic routes for DNA–polymer nanostructures are cumbersome and inefficient, while existing RAFT-PISA systems are restricted to limited monomer types, leading to insufficient core functionality and poor property adjustability. Herein, we present the fabrication of core-functionalized DNA–polymer nanostructures via RAFT-PISA of a thymine-containing monomer in both DMF/water mixed solvent and pure water. Efficient and well-controlled polymerization is achieved by using a DNA-modified chain transfer agent (CTA); however, dense surface DNA chains inhibit structural evolution to form only spherical aggregates. Tuning the surface DNA density and adopting hydrophilic macromolecular CTA enable successful access to spheres, worms, and vesicles by simply regulating core chain lengths. The newly developed core-functionalized DNA–polymer nanostructures retain excellent DNA recognition capability in the shell layer. Meanwhile, they allow programmable post-polymerization morphology modulation through multiple hydrogen bonds in the core layer. This strategy not only provides a reliable approach to constructing distinct DNA–polymer nanostructures but also expands and advances PISA toward tunable core-functionalized nano-objects.